Anticipating Infection: How Parasitism Risk Changes Animal Physiology

Uninfected animals can attempt to prevent parasitism in many ways. Behavioural avoidance of parasitized conspecifics, for instance, is documented in several species. Interactions with parasitized conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well studied, and consequently, less well understood. The way in which exposure to parasitism risk changes the physiology of uninfected animals and the impacts of those changes on animal fitness remain a significant gap in knowledge. Determining how the disease environment experienced by animals impacts their physiology, survival and reproduction has major implications for our knowledge of how parasites affect populations beyond their consumptive effects. If the physiological changes triggered in uninfected animals help reduce disease burden or speed up recovery from disease, they can have cascading effects on disease dynamics; therefore, they are important to study and understand. In this perspective, I highlight studies in vertebrates and invertebrates that demonstrate the existence of these responses. I also consider how these responses may be adaptive and instances when they should occur. Finally, I briefly discuss the importance of studying these responses in relation to animal welfare, human health, disease dynamics and experimental design

We Are Not Alone in Trying to Be Alone

Certain diseases, like colds, tend not to stop us. A paracetamol here, an ibuprofen there, and we are on the go. That is, until we, as a species, are faced with a virus that not only spreads through social contact, but has an estimated reproductive number of 2 to 2.5 and potentially kills 3–4% of those infected (WHO, 2020). To reduce transmission probability of COVID-19, governmental agencies around the world have recommended or enforced measures to decrease social contact; early evidence suggests these measures produce the intended effect (Kucharski et al., 2020)

Wild mice with different social network sizes vary in brain gene expression

Background Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size. Results We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size. Conclusions Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa

Neurotranscriptomic Changes Associated with Chick-directed Parental Care in Adult Non-reproductive Japanese Quail

For many species, parental care critically affects offspring survival. But what drives animals to display parental behaviours towards young? In mammals, pregnancy-induced physiological transformations seem key in preparing the neural circuits that lead towards attraction (and reduced-aggression) to young. Beyond mammalian maternal behaviour, knowledge of the neural mechanisms that underlie young-directed parental care is severely lacking. We took advantage of a domesticated bird species, the Japanese quail, for which parental behaviour towards chicks can be induced in virgin non-reproductive adults through a sensitization procedure, a process that is not effective in all animals. We used the variation in parental responses to study neural transcriptomic changes associated with the sensitization procedure itself and with the outcome of the procedure (i.e., presence of parental behaviours). We found differences in gene expression in the hypothalamus and bed nucleus of the stria terminalis, but not the nucleus taeniae. Two genes identified are of particular interest. One is neurotensin, previously only demonstrated to be causally associated with maternal care in mammals. The other one is urocortin 3, causally demonstrated to affect young-directed neglect and aggression in mammals. Because our studies were conducted in animals that were reproductively quiescent, our results reflect core neural changes that may be associated with avian young-directed care independently of extensive hormonal stimulation. Our work opens new avenues of research into understanding the neural basis of parental care in non-placental species

The Effect of Infection Risk on Female Blood Transcriptomics

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance behaviors) and that their blood would show activation of immune and stress responses. We used female Japanese quail as a study system because they have been shown to respond to male traits, in terms of their own physiology and egg investment. Only two genes showed significant differential expression due to treatment, including an increase in the threonine dehydrogenase (TDH) transcript, an enzyme important for threonine breakdown. However, hundreds of genes in pathways related to activation of immune responses showed coordinated up-regulation in females exposed to immune-challenged males. Suppressed pathways revealed potential changes to metabolism and reduced responsiveness to glucocorticoids. Contrary to our prediction, we found that females paired with immune-challenged males increased food consumption. Water consumption was not changed by treatment. These findings suggest that even short exposure to diseased conspecifics can trigger both behavioral and physiological responses in healthy animals

Rapid Experimental Evolution of Pesticide Resistance in C. elegans Entails No Costs and Affects the Mating System

Pesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides

Sickness Behaviors Across Vertebrate Taxa: Proximate and Ultimate Mechanisms

There is nothing like a pandemic to get the world thinking about how infectious diseases affect individual behavior. In this respect, sick animals can behave in ways that are dramatically different from healthy animals: altered social interactions and changes to patterns of eating and drinking are all hallmarks of sickness. As a result, behavioral changes associated with inflammatory responses (i.e. sickness behaviors) have important implications for disease spread by affecting contacts with others and with common resources, including water and/or sleeping sites. In this Review, we summarize the behavioral modifications, including changes to thermoregulatory behaviors, known to occur in vertebrates during infection, with an emphasis on non-mammalian taxa, which have historically received less attention. We then outline and discuss our current understanding of the changes in physiology associated with the production of these behaviors and highlight areas where more research is needed, including an exploration of individual and sex differences in the acute phase response and a greater understanding of the ecophysiological implications of sickness behaviors for disease at the population level

Immune-Endocrine Links to Gregariousness in Wild House Mice

Social interactions are critically important for survival and impact overall-health, but also impose costs on animals, such as exposure to contagious agents. The immune system can play a critical role in modulating social behavior when animals are sick, as has been demonstrated within the context of “sickness behaviors.” Can immune molecules affect or be affected by social interactions even when animals are not sick, therefore serving a role in mediating pathogen exposure? We tested whether markers of immune function in both the blood and the brain are associated with gregariousness, quantified as number of animals interacted with per day. To do this, we used remote tracking of social interactions of a wild population of house mice (Mus musculus domesticus) to categorize animals in terms of gregariousness. Blood, hair, brain and other tissue samples from animals with extreme gregariousness phenotypes were collected. We then tested whether the levels of three important cytokines (TNF-a, IFN-g and IL- 1b) in the serum, cortex and hypothalamus of these animals could be explained by the gregariousness phenotype and/or sex of the mice. Using the hair as a long-term quantification of steroid hormones, we also tested whether corticosterone, progesterone and testosterone differed by social phenotype. We found main effects of gregariousness and sex on the serum levels of TNF-a, but not on IFN-g or IL-1b. Brain gene expression levels were not different between phenotypes. All hair steroids tended to be elevated in animals of high gregariousness phenotype, independent of sex. In sum, elements of the immune system may be associated with gregariousness, even outside of major disease events. These results extend our knowledge of the role that immune signals have in contributing to the regulation of social behaviors outside periods of illness

Female Presence Does Not Increase Testosterone but Still Ameliorates Sickness Behaviours in Male Japanese Quail

Infections can dramatically modify animal behaviour. The extent of these changes depends on an animal\u27s environment. It has been proposed that testosterone modulates the suppression of behavioural symptoms of sickness under certain reproductive contexts. To further understand the role played by testosterone in modulating sickness behaviours under reproductive contexts, we studied a species, the Japanese quail, in which female exposure rapidly decreases circulating testosterone in males. Males received either an immune challenge (lipopolysaccharide – LPS) or a control injection and their behaviours, mass change and testosterone levels were quantified in the presence or absence of a female. Both the presence of a female and LPS treatment reduced testosterone levels. LPS-treated males maintained in isolation expressed expected sickness behaviours, including increased resting (quantified as crouching) and decreased food and water intake. Despite the reduction in testosterone, when paired with females LPS-treated males showed similar amounts of mating behaviours to controls and reduced crouching. In sum, even under very low levels of testosterone, male quail had reduced sickness behaviours when exposed to females, indicating that testosterone may not be key in modulating sickness behaviours, at least in this species

Oxytocin administration during early pair formation delays communal nursing in female house mice

Oxytocin manipulation has been implicated in the facilitation of social and cooperative behaviours, either through increasing positive and cooperative social interactions, or facilitating bond formation. Here we aimed to determine whether peripheral administration of oxytocin would affect the propensity of unrelated female house mice (Mus musculus domesticus) to cooperate. In order to investigate this we used female house mice, with their cooperative ability to communally nurse offspring. Pairs of unfamiliar females received intraperitoneal injections of oxytocin over a three-day cohabitation period. Following this initial phase, a male was introduced and they were allowed to reproduce. We monitored how long it took females to establish and successfully cooperate in the raising of a communal litter. Oxytocin did not affect the females’ ability to reproduce. However, oxytocin treated females took significantly longer to establish a successful communal litter (with pups of both partners being weaned) than saline treated control females. This delay in communal nursing was due to higher pup mortality and loss of first-born litters in the oxytocin group during their first reproductive event. We conclude that administration of exogenous oxytocin during the early stages of the female relationship delays the tendency of female house mice to affiliate and cooperate in the formation of a communal litter. Our findings contribute to the growing field of oxytocin based studies and sheds light on the potential long term effects of oxytocin during early pairwise social interactions